Process of preparing etheric acetals of 3,4-methylenedioxybenzaldehyde



United States Patent 01 E'fice' 3,506,685 Patented Apr. 14, 19703,506,685 PROCESS OF PREPARING ETHERIC ACETALS OF3,4-METHYLENEDIOXYBENZALDEHYDE John D. Johnson, Kent, Egbert M. Gibbs,London, and Neville Unwin, Surbition, Surrey, England, assignors to BushBoake Allen Limited, London, England, a British company No Drawing.Filed Nov. 26, 1968, Ser. No. 779,270 Int. Cl. C07d 13/10 US. Cl.260-3403 7 Claims ABSTRACT OF THE DISCLOSURE Acetals, and particularlyacetals useful as synergists for pyrethrum are prepared by a reaction ofan aromatic aldehyde such as 3,4 methylenedioxybenzaldehyde with alkylether alcohols in a substantial non-polar medium refluxing at atemperature between 120 and 200 C. and consisting essentially of a hydrosaturated hydrocarbon solvent.

The present invention relates to the preparation of acetals and inparticular to the reaction of alkyl ether alcohols with aromaticaldehydes. The invention is of particular value for the preparation ofpyrethrum synergists.

The preparation of acetals is usually achieved by the reaction of twomoles of an alcohol with one mole of an aldehyde in the presence of anacid catalyst, and removal of water from the system, for example byrefluxing with a suitable non-aqueous solvent. It has been discovered,however, that in a few instances the yields obtained from this reactionare too low for it to be commercially feasible, and the product isheavily contaminated with impurities. A particular example which is ofcommercial importance is the preparation of alkyl ether acetals of 3,4methylenedioxybenzaldehyde (also referred to as heliotropin) e.g. theacetal derived from the monobutyl ether of diethylene glycol. Theseacetals are valuable ingredients of insecticidal compositions, andparticularly compositions containing pyrethrum, with which the acetalhas been found to exert a synergistic insecticidal activity (see forexample British Patent 1,085,645). The direct catalysed reaction ofalkylether alcohols with heliotropin gives such poor yields that it hasbeen proposed in British Patent 1,085,- 645 to make the acetalcommercially by a cumbersome and expensive two stage reaction, whichcomprises converting the aldehyde to a dichloride which is reacted withthe sodium salts of the alcohol.

We have now discovered that aldehyde such as heliotropin may be reacteddirectly with alkyl ether alcohols to form acceptable yields of acetal,provided the reaction is effected at 120 to 200 C. in a substantiallynon-polar medium.

As used herein a substantially non polar medium is a solvent systemhaving a polarity no greater than that of a saturated aliphatichydrocarbon, and containing no more than trace quantities of acids,bases or salts, as illustrated in the examples.

Our invention therefore provides a method of preparing acetals whichcomprises reacting an aromatic aldehyde with an alkyl ether alcohol at atemperature between 120 and 200 C. in a substantially non-polar mediumas herein defined, and removing the water evolved from the system.

Preferably, the reaction is effected at substantially atmosphericpressure by refluxing the reactants in a petroleum fraction at arefluxing temperature of between 120 and 200 C., and preferably from 140to 180 C.

Preferably the alkyl ether alcohol has the formula RO(C H O) H where Ris an alkyl group and n and x are integers. R preferably has from 1 to 6carbon atoms in each C H group, n is conveniently 2 or 3 and x ispreferably from 1 to 3 The most preferred alcohol is monobutyldiethylene glycol.

The invention is particularly applicable to the preparation of acetalsof heliotropin. It is preferred, according to our invention to react analkyl ether alcohol of the formula RO(C,,H O) H (wherein n in each C H Ogrout is 2 or 3, x is an integer from 1 to 3 and R is an alkyl grouphaving from 1 to 6 carbon atoms) with heliotropir at a temperature offrom 140 to 180 C. in a substantially non-polar refluxing medium, and toseparate the watei from the system.

Preferably the alkyl ether alcohol has the aforesaid formula wherein nis 2, x is conveniently 2 or 3 and R may be for example n-butyl, propylor ethyl.

We have discovered that, when a single batch of alkyl ether alcohol (forexample monobutyldiethylene glycol) and heliotropin are refluxed at 120to 200 C. in a substantially non-polar medium, yields approaching, butseldom exceeding, 50% may be achieved. However, the unreacted startingmaterials are largely recoverable anc' may be reused, giving yieldswhich may approach for continuous, or repeated batch operations.

Our invention according to its preferred embodiment therefore provides amethod of preparing a pyrethrurr synergist, which comprises refluxingheliotropin with at alkyl ether alcohol in a substantially non-polarmediurr consisting substantially of a petroleum fraction, the mixturehaving a boiling point between and 200 C. separating the water evolvedfrom the system, recovering unreacted starting materials for reuse, andrecovering ar acetal of heliotropin as product.

Surprisingly the presence of small quantities of acids 01 salts, such asare conventionally used to catalyse the formation of acetals, appears tohave no beneficial effect in the method of our invention and generallyresults it reduced yields of acetal. Although traces of certain conventional acetal forming catalysts can be tolerated with out seriousloss, the yield of acetal generally decline: drastically if quantitiesof such catalysts in excess of fev percent by weight are present. Ingeneral therefore Wt prefer to carry out the reaction in a substantiallynon polar solvent in the substantial absence of added pola:

substances.

The nature of the solvent system is critical. If solvent: more polarthan an aliphatic hydrocarbon oil such as 2 petroleum fraction areemployed the yield is greatly re duced. Thus even in solvents of fairlylow polarity sucl as xylene or toluene, it may be difficult orimpossible tc obtain economic yields of the product. Also critical isth( reaction temperature which is commonly determined by the refluxtemperature of the solution. We have fount that the reaction is too slowto give a useful yield at temperatures of 120 C. or below and tends togive a highly impure product at temperatures above 200 C. The pre ferredtemperature range is C. to 180 C. The preferred solvent is a petroleumfraction boiling within thi: range e.g. at 140 to *C. petroleumfraction.

Water may be separated from this system by cohobation. Surprisingly ithas been found that a quantity 0: water approaching the stoichiometricamount for a com plete reaction may sometimes be evolved, even when theyield of product is less than 50%. The majority of the water is evolvedduring the first hour although evolutior continues at a reduced rate forup to seventeen hours. Ir general the highest yields of product areobtained aftel seventeen hours, although the reaction may be stoppecsooner to obtain slightly lower yields of a purer product.

In general it is convenient to employ an excess of alcohol over thestoichiometric proportion of two moles of alcohol to one of aldehydee.g. a 100% excess, but these proportions are not critical and may bevaried within wide limits. For example 4 to 5 times the stoichiometricamount of alcohol may be employed.

It is convenient to reflux the alcohol in the paraflin solvent to driveoff any water, and to add the aldehyde. The mixture may then be refluxeduntil no further evolu- 4 (a) 109.5 g.monobutyl diethylene glycol andheliotropin B.P. 200/0.01 mm. (b) 102 g.acetal, 11 1.4842, B.P. 200/0.02mm.-

250/0.08 mm. (c) 9.5 g.high boiling products.

tion of water occurs. Preferably the unreacted alcohol and 5 (ii) SBP 6250 1 was flu d ith stirring for aldehyde are recovered by distillatlonunder reduced pres- 075 hour during Which Period traces f Water were 1-sure. To isolate the product, distillation under still lower lected in aDean and Stark trap. h li id was ll ed to FY6551"es y conveniently beemployedcool to 60 over 0.75 hour and product (a) above (108 Theinvention will be illustrated by the following examadded The l i was flxed f 25 5 hours (t i P illustrating the Preparation of the acetal,interrupted overnight) during which period Water 3.1 ml.)

0 was collected in the Dean and Stark trap. The resulting clear redsolution was worked up as above C4H00(CH2)20(CH2)20 @112 to yieldproducts CH- (d) 38.5-mostly monobutyl diethylene glycol and helio- 0tro in B.P. 200/0.01 mm. O4H9O(CH2)2O(CH2)2O p 20.5 -2 0.02 EXAMPLE 1(el)m517 g. acetal n 14845, BP 200 40 81 g. of monobutyl diethyleneglycol and 250 mls. of 2 (f) 5,5 g high boilin roduct a paraflin oilhaving a boiling polnt of 140 to 160 0 (iii) As (ii) from SBP 6 (100ml.) and product ((1) sold under the name Shell Spec1al Bolling PointSpirit above (365 heating fo 265 hours to b i water No. 6 (hereinafterreferred to as SBP 6) were gently re- (09 m1) Products worked up asabove Were fluxed with stirring for 0.75 hour during which period 0.5ml. water was collected in a Dean and Stark trap. 38 z h ggg f ggg sg gglycol and he 10 g. heliotropin was added to the hot solution and themixp a o (h) 15.5 g.acetal, n 1.4840, B.P. 200 /0.01 mm. ture refluxedat a temperature of 158 to 160 C. for 17 (1) 2 g.-h1gh boiling products.hours. 4.5 mls. of water collected. The solution was 211- f h lowed tocool to 30 C. and the solvent was recovered by The ylelds of tropltalStamng Products or eac distillation under reduced pressure of 3 to 7 mm.Distilla- 30 stage were t tion of the residue under reduced pressureyielded: i

1 (a) g. monobutyl diethylene glycol and heliotropin (ii) 543 (b) 12 g.monobutyl diethylene glycol, heliotropin and (hi) 44 1 acetal (c) acetal(B.P. 200 to 230 0. at 0.04 mm. yield 48.7% 35 32 an ymld acetal for thethree Stages n 1.4838) (d) 6.5 high boiling residue. EXAMPLE 4 EXAMPLE 2Parts (i) and (ii) of Example 3 were repeated using White Spirit (B.P.ISO-200 C.) as solvent in place of Monobutyl diethylene glycol (81 g.)and SBP 6 (100 40 SBP Yields of 1 ml.) were gently refluxed withstirring for 1.25 hours percent during which period water (0.7 ml.) wascollected in a (i) 405 Dean and Stark trap. The solution was allowed tocool 412 to 90 C. over 0.75 hour and heliotropin (38 g.) added. Thesolution was refluxed for 39 hours (thrice interrupted glvmg an overallyleld of overnight) during which period water (4.6 ml.) was col- EXAMPLE5 lected in the Dean and Stark trap. (The temperature of Monobutyldlelhylene g y gInS equivalent to the solution varied between 168m 73),100% excess), SBP 6 (250 mls.) and heliotropin (38 The resulting redsolution was allowed to cool and the g Were InlXed, brought to the bolllznllnntes and SBP 6 distilled under 7 to 8 mms. pressure. The residue50 g y refluxed for 11/2 hours, during Whlch time was distilled to yield47 g. acetal B.P. 200-30/0.02 mm. water was collected y y of a Dean andStark p- 1 4849 Yi 1d was 41% The solution was allowed to cool to C. andthen again brought to the boil in 7 minutes and refluxing con- EXAMPLE 3tinued for a total period of 20 hours, collecting the water (i)Monobutyl diethylene glycol (162 g.) and SBP 6 55 of reaction in theDean and Stark trap. (500 ml.) were refluxed with stirring for 0.75 hourdur- The solution was allowed to cool overnight and then ing whichperiod water (0.7 ml.) was collected in a Dean partly distilled underreduced pressure to remove the and Stark trap. The solution was allowedto cool to petroleum solvent. The residue was distilled at 1 mm. over0.75 hour and heliotropin (76 g.) added. The solucollecting somerecovered heliotropine and glycol, totion was refluxed for 28 hours(twice interrupted over- 60 gether with tropital fractions B.P.230-250/1 mm. night) during which perlod water (7.6 ml.) was collected(a) gms" assay 86% in the Dean and Stark trap.

(b) 62 gms., assay 100.4% The resulting golden-red clear solution wasallowed to cool and SBP 6 distilled under 3 to 5 mms. pressure. TheYield 59% theory residue was distilled to yield products- 5 EXAMPLES6-15 Reflux time Yield Percent Example Solvent Catalyst hrs. g. yieldR.R.I.

0 SBP6 0.13s gm. NI'I-1N03 44.5 40 40.2 infi l/1844 6 0.151 gm.acetylchloride. 32 47 41 nn"l.4826 0.362 g. perchloric acid. 13.25 38 33.2 Ilrl.4855 1 drop perchloric acid. 30 50 43. 7 nn 1.4832 0.106gtrlchloracetlc ac 33.5 51 44.5 nn 1.4828 0.112 g. piperonylie aeid 4241.5 36.3 nn 1A827 0.25 23 32.5 28.4 1111 14700 5g. 31.5 37 32.3 n11.4s40 4 22 25.5 22.2 no 1A839 None 26.25 45 39.3 nD 1A840 We claim:

1. A method for the manufacture of an acetal which comprises 7 heating3,4-methylenedioxybenzaldehyde and an alkyl ether alcohol of the formulaRO(C H O) H, wherein n is an integer from 2 to 3, x is an integer from 1to 3, and R is an alkyl group having from 1 to 6 carbon atoms, underreflux in a substantially non-polar medium consisting essentially of asaturated hydrocarbon solvent having a boiling point between 120 and 200C.

2. The method according to claim 1 wherein the reaction mixture refluxesat a temperature of 140 to 180 C.

3. The method according to claim 1 wherein the solvent is a petroleumfraction having a boiling point of 140 to 160 C.

4. The method according to claim 1 wherein the alcohol is the monobutylether of diethylene glycol.

5. The method according to claim 1 which comprises heating3,4-methylenedioxybenzaldehyde with said alkyl ether alcohol at refluxtemperature in a substantially nonpolar medium consisting essentially ofa saturated hydrocarbon solvent boiling at a temperature of from to C.,separating water from the system by cohobation, recovering unreactedstarting materials for re-use and recovering an acetal product.

6. The method according to claim 5 wherein the alkyl ether alcohol isemployed in stoichiometric excess of up to 500%.

7. The method according to claim 6 wherein the alcohol is the monobutylether of diethylene glycol.

References Cited Bell et al., Journal of Organic Chemistry, vol. 30(12),1965, pp. 4284-92.

NICHOLAS S. RIZZO, Primary Examiner J. H. TURNIPSEED, Assistant ExaminerUS. Cl. X.R.

' g;;g UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3, 5 5

JOHN D, JOHNSON, EGBERT M, GIBBS, and NEVILLE UNWIN Inventor (s) DatedApril 14, 1970 It: is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

' Column 3, line 35, --56 g,-- should appear following SEA-L) Attest:

Edward M. Fletcher, Ir.

Atlesting Officer SIGNED AN'D SEALED Aus ..1g7

WILLIAM E. Sam I- comissionar of Patent:

